Mechanistic Study of Inspiratory Training in Childhood Asthma

项目摘要/摘要 在儿童中，哮喘是呼吸道症状和缺课的主要原因。通过以下机制 目前尚不清楚，哮喘儿童中的肥胖是哮喘的强烈危险因素，而哮喘更有症状 而且很难管理。在哮喘儿童中，肥胖与对 常规抗炎哮喘药物。因此，更好地理解潜在的 儿童肥胖相关哮喘的发病机制是必要的。发现“肥胖”的机制 为了促进更合适的表型特异性治疗，哮喘是一个紧迫的公共卫生问题 需要。众所周知，无论潜在的哮喘如何，肥胖都会损害呼吸系统的顺应性和 吸气肌肉效率导致呼吸努力的增加。我们实验室在哮喘患者中发现 儿童肥胖与更频繁的哮喘症状和更高的可能性相关 有呼吸困难。吸气训练和其他形式的康复在成年人中很常见，但 正在攻读儿科学的学生。吸气式‘康复’训练(IT)最近在这两个地方都有表现 减少儿童和成人的呼吸困难和哮喘症状。我们的研究团队发现它在6周内 耐受性良好，并导致吸气功能改善和临床趋势持续改善 在哮喘儿童中采取的措施。我们建议的MICA(力学研究)的中心目标 吸气训练在儿童哮喘中的作用)研究是为了测量8周的IT对 吸气功能(力量和耐力)和小气道功能障碍的示波法测定 6-17岁的哮喘患者--有没有肥胖。我们的中心假设是肥胖会促进 吸气肌疲劳和小气道功能障碍，它将缓解这些机制。 在一项掩蔽的平行ARM试验中，75名患有哮喘的青年(一半患有肥胖症)将被随机分为两组 (低剂量或高剂量)或假手术对照8周。吸气强度和耐力，小气道 将在基线和IT后评估功能障碍(SAD)和运动能力。目标1将描述 吸气疲劳和SAD在肥胖相关性哮喘中的作用目标2将决定 信息技术对吸气肌疲劳的影响。目标3将确定IT对小气道的影响 功能障碍。MICA的研究将通过以下方式提供有关儿童“肥胖哮喘”的机制知识 根据肥胖状况比较治疗反应。吸气肌功能变化的测量 与症状肥胖相关的儿童在短期治疗后的小气道功能障碍 哮喘将对肥胖恶化的潜在机制提供亟需的理解 儿童哮喘；并将揭示一种安全的非 药物干预将为更大规模的第三阶段试验铺平道路。

PROJECT SUMMARY/ABSTRACT In children, asthma is a leading cause of respiratory symptoms and missed school. By mechanisms that are unclear, obesity in children with asthma is a strong risk factor for asthma that is more symptomatic and difficult to manage. Among asthmatic children, obesity is associated with a reduced response to conventional anti-inflammatory asthma drugs. Therefore, a better understanding of the underlying mechanisms of obesity-related asthma in children is needed. Discovering the mechanisms of `obese asthma' in order to foster more appropriate phenotype-specific therapies is a pressing public health need. Obesity, regardless of underlying asthma, is known to impair respiratory system compliance and inspiratory muscle efficiency leading to increases in the effort of respiration. Our lab found in asthmatic children that obesity is associated with more frequent asthma symptoms and a higher likelihood of having dyspnea. Inspiratory training and other forms of rehabilitation are common in adults but is understudied in pediatrics. Inspiratory `rehabilitation' training (IT) recently has been shown in both children and adults to reduce dyspnea and asthma symptoms. Our research team found IT over 6 weeks was well-tolerated, and led to improved inspiratory function and consistently improved trends in clinical measures, among children with asthma. The central objective of our proposed MICA (Mechanistic Study of Inspiratory Training in Childhood Asthma) study is to measure the effects of 8-weeks of IT on inspiratory function (strength and endurance) and small airway dysfunction measured by oscillometry in 6-17 year olds with asthma - with and without obesity. Our central hypothesis is that obesity promotes inspiratory muscle fatigue and small airway dysfunction, and that IT will mitigate these mechanisms. In a masked parallel arm trial, 75 youths with asthma (half with obesity) will be randomized to either IT (low or high dose) or SHAM control for 8-weeks. Inspiratory strength and endurance, small airway dysfunction (SAD), and exercise capacity will be assessed at baseline and after IT. Aim 1 will describe the contributions of inspiratory fatigue and SAD to obesity-related asthma. Aim 2 will determine the effects of IT on inspiratory muscle fatigue. Aim 3 will determine the effects of IT on small airway dysfunction. The MICA study will provide mechanistic knowledge about pediatric `obese asthma' by comparing treatment responses by obesity status. Measuring the changes in inspiratory muscle function and small airways dysfunction following a short regimen IT in children with symptomatic obesity-related asthma will provide much needed understanding about mechanisms underlying how obesity worsens asthma in children; and will uncover mechanisms and optimal dosing intensity involved in a safe non- drug intervention that will pave the way for larger phase III trials.